Zoonotic cutaneous leishmaniasis (ZCL) is a vector-borne disease caused by Leishmania major, transmitted by the bites of phlebotomine sand flies. The fat sand rat (Psammomys obesus) and the desert's gird (Meriones shawi ) are the main reservoir hosts of this parasite. Cutaneous leishmaniasis is considered by the WHO to be a neglected tropical disease, affecting about 1.5 million people per year worldwide. The disease is widespread in Central and South America, the Mediterranean basin, and the near and far east countries where it is strongly correlated with poverty. Although ZCL is not fatal, the lesions produced may cause substantial disfigurement and severe distress to infected individuals with lifelong psychological and social consequences. No vaccine is available and treatment of humans is largely based on chemical therapy (pentavalent antimony/glucantime). To date, resistance of L. major to glucantime, the only affordable drug in developing countries for more than 40 years, has become a major concern. New alternatives to control ZCL are urgently needed. In Tunisia, ZCL is a peridomestic disease endemic in rural areas with low socio-economic status with an annual incidence rate of 669.7/100,000 per year. Phlebotomus papatasi is the main vector of L. major in Tunisia and in North Africa. Only chemical therapy with glucantime is currently available, with neither vector nor dog control programs. Killing or diverting infected sand flies from humans can reduce the transmission of ZCL. Although indoor residual spraying (IRS) of insecticides is effective in reducing the incidence of ZCL, it requires expensive yearly applications and its applicability is thus limited by financial constraints in low income countries. Insecticide-treated curtains or bednets offer effective protection against P. papatasi; but transmission continues as before after cessation of these measures. Despite their efficacy in the interruption of ZCL transmission, programs based on the distribution of ITNs are poorly implemented in many endemic countries and are beyond the means of many families in ZCL-endemic villages. Although poisoning ZCL rodent reservoirs with zinc phosphide has reduced the incidence of ZCL, this approach is ecologically unsound. We aim to develop a sustainable method based on diverting sand fly vectors from humans to reduce the transmission of ZCL in endemic areas. Numerous studies show that host diversity could reduce the incidence of zoonotic vector- borne diseases by a dilution effect. A high species diversity in the community of vector hosts reduces the infection prevalence or abundance of the vectors by diluting the effects of the most competent disease reservoir and subsequently reducing the incidence of the disease. Zooprophylaxis is the use of wild or domestic animals, which are not reservoir hosts of a given diseases, to deflect vectors from humans creating a dilution effect. The presence of livestock around houses may diminish transmission of the disease and protect humans from the bites of infected sand flies. Our preliminary studies have shown that breeding rabbits in artificia burrows located in peri-domestic areas significantly reduces the indoor abundance of P. papatasi within houses. Rabbits strongly attract sand flies but are a dead-end host for L. major. We hypothesize that rabbits bred in man-made underground holes located in the peri-domestic areas act as a dilution hosts and exert a zooprophylactic effects on the transmission of ZCL in endemic areas. The objective of this proposal is to establish a new vector control strategy based on zooprophylaxis to reduce transmission of ZCL in endemic focus. This program will be validated in Tunisia for several reasons: (1) endemicity of disease; (2) limited current control options; (3) access to laboratory models and field sites for testing intervention strategies; and (4) ability to conduct field-based research in a representative region that is stable politically. Indeed, lessons learned from this project should impact public health policy authorities in the politically sensitive Middle East and North African (MENA) nations. This two-year project will develop a new approach to control ZCL transmission built upon the transfer of expertise from the US to Tunisia, fostering both capacity building and innovation.